The hormone analog 1-deamino-8-D-arginine vasopressin (desmopressin, hereinafter also abbreviated "DDAVP") is an important medicine for the treatment of diurea, such as associated with diabetes insipidus and nocturnal enuresis, and urine incontinence, and for the treatment of bleeding disorders such as hemophilia A, von Willebrand's disease and other conditions associated with platelet dysfunction.
Medium-size peptides can be routinely produced by a variety of multi-step techniques in moderately pure form. Their impurity pattern and, thus, measures to be taken for their purification depend on the purity of reactants and reagents, the particular route of synthesis and reaction conditions in general.
This further purification, however, often requires highly efficient purification methods, such as electrophoresis, or other methods which can only handle small amounts of peptide in a single run. Extensive purification also has a tendency to reduce yield, particularly when applied in the final synthetic steps.
These considerations also apply to the synthesis of DDAVP, which is usually isolated and medically used in form of its acetate. While single batches of pure DDAVP thus may be obtained by use of conventional methods of synthesis and purification, the scale in which single batches of DDAVP can be prepared by these methods is unsatisfactory from an economic standpoint. In this specification, the term "single batch of DDAVP" signifies the DDAVP obtained in one single final step of DDAVP synthesis and purification. In view of the complexity of synthesis of DDAVP and other medium-size peptides, and also because of their often extremely high biologic activity, such single batch of substantial size is a batch containing product in the order of 500 g.
As rule, single DDAVP batches differ in, i.e., DDAVP-content and pattern of impurities. Documentation requirements for single batches, no matter whether small or large, include DDAVP-assay and tests such as specific optical rotation, absorbance, amino acid composition, content of related peptides, acetic acid and water. Since cost for analysis is substantial and identical for batches of all sizes, the production of DDAVP in single batches of substantial size, and DDAVP thus produced is desirable. There is, of course, also the usual benefit of economics of scale in producing high-purity DDAVP in single batches of substantial size.